Association of Alkaline Phosphatase with Cardiovascular Disease in Patients with Dyslipidemia: A 6-Year Retrospective Study.

BACKGROUND AND AIM: Serum alkaline phosphatase (ALP) activity has been associated with atherosclerotic cardiovascular disease (ASCVD). We aimed to investigate the association of ALP with ASCVD in patients with dyslipidemia. METHODS: We conducted a retrospective cohort study including consecutive adults with dyslipidemia followed-up for ≥3 years (from 1999 to 2022) in the outpatient Lipid Clinic of Ioannina University General Hospital, Greece. The primary endpoint was the association between baseline ALP and incident ASCVD after adjusting for traditional risk factors (i.e., sex, age, hypertension, diabetes, smoking, and dyslipidemia), baseline ASCVD, and lipid-lowering treatment. ALP levels were stratified by tertiles as follows: low: <67 U/L, middle: 67-79 U/L, high: ≥79 U/L. RESULTS: Overall, 1178 subjects were included; 44% were males, and their median age was 57 years (range: 49-65). During a 6-year median follow-up (interquartile range: IQR: 4-9), 78 new ASCVD events (6.6%) occurred. A statistically significant association between baseline ALP levels and incident ASCVD was demonstrated (Odds Ratio, OR: 6.99; 95% Confidence Interval, CI: 2.29-21.03, p = 0.001). Subjects in the highest ALP tertile had the highest odds for ASCVD when compared with those in the lowest tertile (OR: 2.35; 95% CI: 1.24-4.41, p = 0.008). CONCLUSIONS: The present study indicates an association between ALP and the development of ASCVD in patients with dyslipidemia, which underscores the potential of ALP as a predictive tool or a therapeutic target in the realm of ASCVD prevention within this population.

Familial hypercholesterolemia and its manifestations: Practical considerations for general practitioners.

Familial hypercholesterolemia (FH) is the most common genetic disorder of lipid metabolism, affecting almost 1 in 250 individuals worldwide. It is usually inherited via the autosomal dominant way and is characterized by aberrantly high total and low-density lipoprotein cholesterol (LDL-C) concentrations from early childhood, predisposing to increased risk of premature atherosclerotic cardiovascular disease (ASCVD), mostly coronary heart disease (CHD). Despite its high prevalence in the general population and the high ASCVD risk, FH is often underdiagnosed and undertreated. Genetic diagnosis is not always necessary since specific criteria, taking into account the patient's individual and family history, clinical signs, and untreated LDL-C concentrations, may be used for prompt diagnosis. Except for CHD, which may be already evident at diagnosis, leading to increased mortality, other non-CHD morbidities, such as stroke, peripheral artery disease, carotid artery stenosis, and aortic valve calcification may be also present, substantiating the need for prompt intervention. Statins constitute the mainstay of treatment both in adults and children >8 years old. In cases of statin intolerance or not achieving the LDL-C target despite maximally tolerated statin dose, ezetimibe and/or proprotein convertase subtilisin-kexin type 9 inhibitors may be used. The advent of recently approved medications, such as inclisiran and bempedoic acid, either as monotherapy or as add-on therapy to statins, has further enhanced the therapeutic armamentarium that can be used in FH patients. The purpose of this narrative review is to provide practical considerations regarding the diagnostic and therapeutic approach to FH patients.

Effects of Lipid-Modifying and Other Drugs on Lipoprotein(a) Levels-Potent Clinical Implications.

The past few years have shown an ongoing interest in lipoprotein(a) (Lp(a)), a lipid molecule that has been proven to have atherogenic, thrombogenic, and inflammatory properties. Several lines of evidence, indeed, have demonstrated an increased risk of cardiovascular disease as well as calcific aortic valve stenosis in patients with elevated Lp(a) levels. Statins, the mainstay of lipid-lowering therapy, slightly increase Lp(a) levels, while most other lipid-modifying agents do not significantly alter Lp(a) concentrations, except for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. The latter have been shown to reduce Lp(a) levels; however, the clinical significance of this effect has not been clearly elucidated. Of note, the pharmaceutical lowering of Lp(a) may be achieved with novel treatments specifically designed for this purpose (i.e., antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs)). Large clinical trials with cardiovascular outcomes with these agents are ongoing, and their results are eagerly awaited. Furthermore, several non-lipid-modifying drugs of various classes may influence Lp(a) concentrations. We have searched MEDLINE, EMBASE, and CENTRAL databases up to 28 January 2023 and summarized the effects of established and emerging lipid-modifying drugs and other medications on Lp(a) levels. We also discuss the potent clinical implications of these alterations.

Egg Consumption, Cardiovascular Disease and Cardiometabolic Risk Factors: The Interaction with Saturated Fatty Acids. Results from the ATTICA Cohort Study (2002-2012).

Purpose: To examine the association of egg intake with 10-year risk of cardiovascular disease (CVD) and other cardiometabolic risk factors in a sample of individuals of Mediterranean origin. Methods: In 2001−2002, n = 1514 men and n = 1528 women (>18 years old) from the greater Athens area, Greece, were enrolled. Information on any egg intake, eaten as a whole, partly or in recipes was assessed via a validated semi-quantitative food frequency questionnaire. Follow-up for CVD evaluation (2011−2012) was achieved in n = 2020 participants (n = 317 CVD cases). Results: Ranking from lowest (<1 serving/week) to intermediate (1−4 servings/week) and high (4−7 servings/week) egg consumption tertiles, lower CVD incidence was observed (18%, 9% and 8%, respectively, p-for-trend = 0.004). Unadjusted analysis revealed that 1−3 eggs/week and 4−7 eggs/week were associated with a 60% and 75%, respectively, lower risk of developing CVD compared with the reference group (<1 egg/week). When adjusting for sociodemographic, lifestyle and clinical factors, significance was retained only for 1−3 eggs/week (hazard ratio (HR) = 0.53, 95% confidence interval (95% CI) = 0.28, 1.00). When total saturated fatty acid (SFA) intake was taken into account, this inverse association was non-significant. Multi-adjusted analysis revealed that in participants of low SFA intake, 1 serving/day increase in egg intake resulted in 45% lower risk of developing CVD. In the case of higher SFA consumption, only 1−3 eggs/week seemed to protect against CVD (HR = 0.25, 95% CI = 0.07, 0.86). In the case of intermediate cardiometabolic disorders, no significant trend was observed. Conclusions: Overall dietary habits principally in terms of SFA intake may be detrimental to define the role of eggs in cardiac health.

Hyponatremia in Patients with Heart Failure beyond the Neurohormonal Activation Associated with Reduced Cardiac Output: A Holistic Approach.

BACKGROUND: Heart failure (HF) is considered an epidemic disease with considerable morbidity, mortality, and immense healthcare costs. Electrolyte abnormalities are often encountered in patients with HF, posing a diagnostic and therapeutic challenge for clinicians. Hyponatremia affects up to one-third of HF patients and represents an unfavorable prognostic factor. SUMMARY: Low sodium levels in HF are mainly attributed to the neurohormonal activation secondary to decreased effective circulating volume. However, patients with HF often have several comorbidities which may cause or exacerbate the preexisting hyponatremia. Factors that provoke HF, such as alcohol overconsumption, may also be involved in hyponatremia development. Furthermore, drugs which are frequently prescribed to HF patients, especially diuretics, are potential culprits of hyponatremia and should always be addressed since their withdrawal may reverse hyponatremia. Despite the great prevalence and deleterious effects of hyponatremia in these patients, it is often overlooked and consequently undertreated. In this review, we present the mechanisms involved in the development of hyponatremia focusing on those besides neurohormonal activation. We also discuss the proper management of this electrolyte disorder which is frequently complex in patients with HF. KEY MESSAGES: Hyponatremia in patients with HF is not only the result of neurohormonal activation; several comorbidities and frequently used drugs should also be addressed. Hence, a holistic approach is required both for the diagnosis and optimal treatment.

Progressive, Qualitative, and Quantitative Alterations in HDL Lipidome from Healthy Subjects to Patients with Prediabetes and Type 2 Diabetes.

Prediabetes is a clinically silent, insulin-resistant state with increased risk for the development of type 2 diabetes (T2D) and cardiovascular disease (CVD). Since glucose homeostasis and lipid metabolism are highly intersected and interrelated, an in-depth characterization of qualitative and quantitative abnormalities in lipoproteins could unravel the metabolic pathways underlying the progression of prediabetes to T2D and also the proneness of these patients to developing premature atherosclerosis. We investigated the HDL lipidome in 40 patients with prediabetes and compared it to that of 40 normoglycemic individuals and 40 patients with established T2D using Nuclear Magnetic Resonance (NMR) spectroscopy. Patients with prediabetes presented significant qualitative and quantitative alterations, potentially atherogenic, in HDL lipidome compared to normoglycemic characterized by higher percentages of free cholesterol and triglycerides, whereas phospholipids were lower. Glycerophospholipids and ether glycerolipids were significantly lower in prediabetic compared to normoglycemic individuals, whereas sphingolipids were significantly higher. In prediabetes, lipids were esterified with saturated rather than unsaturated fatty acids. These changes are qualitatively similar, but quantitatively milder, than those found in patients with T2D. We conclude that the detailed characterization of the HDL lipid profile bears a potential to identify patients with subtle (but still proatherogenic) abnormalities who are at high risk for development of T2D and CVD.

Early Investigational and Experimental Therapeutics for the Treatment of Hypertriglyceridemia.

Hypertriglyceridemia has been identified as a risk factor for cardiovascular disease and acute pancreatitis. To date, there are only few drug classes targeting triglyceride levels such as fibrates and ω-3 fatty acids. These agents are at times insufficient to address very high triglycerides and the residual cardiovascular risk in patients with mixed dyslipidemia. To address this unmet clinical need, novel triglyceride-lowering agents have been in different phases of early clinical development. In this review, the latest and experimental therapies for the management of hypertriglyceridemia are presented. Specifically, ongoing trials evaluating novel apolipoprotein C-III inhibitors, ω-3 fatty acids, as well as fibroblast growth 21 analogues are discussed.

Role of dipeptidyl peptidase 4 inhibitors in the new era of antidiabetic treatment.

The last few years important changes have occurred in the field of diabetes treatment. The priority in the therapy of patients with diabetes is not glycemic control per se rather an overall management of risk factors, while individualization of glycemic target is suggested. Furthermore, regulatory authorities now require evidence of cardiovascular (CV) safety in order to approve new antidiabetic agents. The most novel drug classes, i.e., sodium-glucose transporter 2 inhibitors (SGLT2-i) and some glucagon-like peptide-1 receptor agonists (GLP-1 RA), have been demonstrated to reduce major adverse CV events and, thus, have a prominent position in the therapeutic algorithm of hyperglycemia. In this context, the role of previously used hypoglycemic agents, including dipeptidyl peptidase 4 (DPP-4) inhibitors, has been modified. DPP-4 inhibitors have a favorable safety profile, do not cause hypoglycemia or weight gain and do not require dose uptitration. Furthermore, they can be administered in patients with chronic kidney disease after dose modification and elderly patients with diabetes. Still, though, they have been undermined to a third line therapeutic choice as they have not been shown to reduce CV events as is the case with SGLT2-i and GLP-1 RA. Overall, DPP-4 inhibitors appear to have a place in the management of patients with diabetes as a safe class of oral glucose lowering agents with great experience in their use.

Bone Health in Patients with Dyslipidemias: An Underestimated Aspect.

Beyond being aging-related diseases, atherosclerosis and osteoporosis share common pathogenetic pathways implicated in bone and vascular mineralization. However, the contributory role of dyslipidemia in this interplay is less documented. The purpose of this narrative review is to provide epidemiological evidence regarding the prevalence of bone disease (osteoporosis, fracture risk) in patients with dyslipidemias and to discuss potential common pathophysiological mechanisms linking osteoporosis and atherosclerosis. The effect of hypolipidemic therapy on bone metabolism is also discussed. Despite the high data heterogeneity and the variable quality of studies, dyslipidemia, mainly elevated total and low-density lipoprotein cholesterol concentrations, is associated with low bone mass and increased fracture risk. This effect may be mediated directly by the increased oxidative stress and systemic inflammation associated with dyslipidemia, leading to increased osteoclastic activity and reduced bone formation. Moreover, factors such as estrogen, vitamin D and K deficiency, and increased concentrations of parathyroid hormone, homocysteine and lipid oxidation products, can also contribute. Regarding the effect of hypolipidemic medications on bone metabolism, statins may slightly increase BMD and reduce fracture risk, although the evidence is not robust, as it is for omega-3 fatty acids. No evidence exists for the effects of ezetimibe, fibrates, and niacin. In any case, more prospective studies are needed further to elucidate the association between lipids and bone strength.

Lipoprotein (a) as a treatment target for cardiovascular disease prevention and related therapeutic strategies: a critical overview.

Advances in several fields of cardiovascular (CV) medicine have produced new treatments (e.g. to treat dyslipidaemia) that have proven efficacy in terms of reducing deaths and providing a better quality of life. However, the burden of CV disease (CVD) remains high. Thus, there is a need to search for new treatment targets. Lipoprotein (a) [Lp(a)] has emerged as a potential novel target since there is evidence that it contributes to CVD events. In this narrative review, we present the current evidence of the potential causal relationship between Lp(a) and CVD and discuss the likely magnitude of Lp(a) lowering required to produce a clinical benefit. We also consider current and investigational treatments targeting Lp(a), along with the potential cost of these interventions.

Immunomodulation and Reduction of Thromboembolic Risk in Hospitalized COVID-19 Patients: Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND: We aimed to investigate the potential beneficial effect of immunomodulation therapy on the thromboembolic risk in hospitalized COVID-19 patients. METHODS: We searched PubMed and Scopus for randomized trials reporting the outcomes of venous thromboembolism (VTE), ischemic stroke or systemic embolism, myocardial infarction, any thromboembolic event, and all-cause mortality in COVID-19 patients treated with immunomodulatory agents. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using the Mantel-Haenszel random effects method. RESULTS: Among 8499 patients hospitalized with COVID-19, 4638 were treated with an immunomodulatory agent, 3861-with usual care only. Among the patients prescribed immunomodulatory agents, there were 1.77 VTEs per 100 patient-months compared to 2.30 among those treated with usual care (OR: 0.84, 95% CI: 0.61-1.16; I2: 0%). Among the patients who received an interleukin 6 (IL-6) antagonist, VTEs were reported in 12 among the 1075 patients compared to 20 among the 848 receiving the usual care (OR: 0.52, 95% CI: 0.22-1.20; I2: 6%). Immunomodulators as an add-on to usual care did not reduce the risk of stroke or systemic embolism (OR: 1.10, 95% CI: 0.50-2.40; I2: 0%) or of myocardial infarction (OR: 1.06, 95% CI: 0.47-2.39; I2: 0%) and there was a nonsignificant reduction in any thromboembolic event (OR: 0.86, 95% CI: 0.65-1.14; I2: 0%). CONCLUSIONS: We did not identify a statistically significant effect of immunomodulation on prevention of thromboembolic events in COVID-19. However, given the large effect estimate for VTE prevention, especially in the patients treated with IL-6 antagonists, we cannot exclude a potential effect of immunomodulation.

An overview of diagnosis and management of drug-induced hypomagnesemia.

Magnesium (Mg) is commonly addressed as the "forgotten ion" in medicine. Nonetheless, hypomagnesemia should be suspected in clinical practice in patients with relevant symptomatology and also be considered a predisposing factor for the development of other electrolyte disturbances. Furthermore, chronic hypomagnesemia has been associated with diabetes mellitus and cardiovascular disease. Hypomagnesemia as a consequence of drug therapy is relatively common, with the list of drugs inducing low serum Mg levels expanding. Culprit medications linked to hypomagnesemia include antibiotics (e.g. aminoglycosides, amphotericin B), diuretics, antineoplastic drugs (cisplatin and cetuximab), calcineurin inhibitors, and proton pump inhibitors. In recent years, the mechanisms of drug-induced hypomagnesemia have been unraveled through the discovery of key Mg transporters in the gut and kidney. This narrative review of available literature focuses on the pathogenetic mechanisms underlying drug-induced hypomagnesemia in order to increase the insight of clinicians toward early diagnosis and effective management.

Hyperemesis Gravidarum: A Benign Condition of Pregnancy or a Challenging Metabolic Disorder?

Hyperemesis gravidarum (HG) is a complication mainly of the first trimester of pregnancy, which sometimes leads to metabolic disorders such as hypovolemia and acute kidney injury (AKI). Herein, we present the case of a 25-year-old woman at week 10 of gestation who exhibited a constellation ofsevere abnormalities, namely AKI (serum creatinine 6.15 mg/dl), transaminasemia (serum aminotransferases >1,000 IU/l), alkalemia (arterial pH7.667), hyponatremia (serum sodium 117 mEq/l), hypochloremia (serum chloride 54 mEq/l), hypokalemia (serum potassium 2.2 mEq/l) and hyperuricemia (serum uric acid 20 mg/dl). Despite a thorough work-up, no other disorder was found apart from HG. All symptoms and metabolic abnormalities resolved with targeted administration of intravenous fluids. The differential diagnosis of these disorders and therapeutic challenges are discussed. LEARNING POINTS: Hyperemesis gravidarum is a severe form of vomiting during pregnancy that typically occurs in the first trimester.It may lead to severe metabolic abnormalities including acute kidney injury (AKI), and electrolyte and acid-base disturbances.Early detection, thorough diagnostic evaluation and prompt management with fluid resuscitation are essential for the well-being of both the mother and the fetus.

Hyponatremia in Patients with Hematologic Diseases.

Hyponatremia is the most common electrolyte disorder in clinical practice and is associated with increased morbidity and mortality. It is frequently encountered in hematologic patients with either benign or malignant diseases. Several underlying mechanisms, such as hypovolemia, infections, toxins, renal, endocrine, cardiac, and liver disorders, as well as the use of certain drugs appear to be involved in the development or the persistence of hyponatremia. This review describes the pathophysiology of hyponatremia and discusses thoroughly the contributing factors and mechanisms that may be encountered specifically in patients with hematologic disorders. The involvement of the syndrome of inappropriate antidiuretic hormone (SIADH) secretion and renal salt wasting syndrome (RSWS) in the development of hyponatremia in such patients, as well as their differential diagnosis and management, are also presented. Furthermore, the distinction between true hyponatremia and pseudohyponatremia is explained. Finally, a practical algorithm for the evaluation of hyponatremia in hematologic patients, as well as the principles of hyponatremia management, are included in this review.

Metabolic consequences of immune checkpoint inhibitors: A new challenge in clinical practice.

Treatment of oncologic patients has progressed greatly the last few years with the development of immune checkpoint inhibitors (ICPIs). These drugs are associated with the immune system and, thus, may cause side effects of immune origin, the so called immune related adverse events (irAEs). Immune related AEs may actually affect all organs and systems and frequently resemble clinical entities commonly encountered in clinical practice. As ICPIs have improved both quality of life and life expectancy, clinicians of various specialties may need to deal with irAEs in their everyday practice. Therefore, they should be able to recognize them timely and treat them accordingly. Herein, we review the pathophysiology, clinical manifestations and treatment of irAEs.

Achieving low-density lipoprotein cholesterol targets as assessed by different methods in patients with familial hypercholesterolemia: an analysis from the HELLAS-FH registry.

BACKGROUND: Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and increased cardiovascular disease (CVD) risk. FH patients often have increased lipoprotein(a) [Lp(a)] levels, which further increase CVD risk. Novel methods for accurately calculating LDL-C have been proposed. METHODS: Patients with FH were recruited by a network of Greek sites participating in the HELLAS-FH registry. LDL-C levels were calculated using the Friedewald (LDL-CF) and the Martin/Hopkins (LDL-CM/H) equations as well as after correcting LDL-CM/H for Lp(a) levels [LDL-CLp(a)corM/H]. The objective was to compare LDL-C levels and target achievement as estimated by different methods in FH patients. RESULTS: This analysis included 1620 patients (1423 adults and 197 children). In adults at diagnosis, LDL-CF and LDL-CM/H levels were similar [235 ± 70 mg/dL (6.1 ± 1.8 mmol/L) vs 235 ± 69 mg/dL (6.1 ± 1.8 mmol/L), respectively; P = NS], while LDL-CLp(a)corM/H levels were non-significantly lower than LDL-CF [211 ± 61 mg/dL (5.5 ± 1.6 mmol/L); P = 0.432]. In treated adults (n = 966) both LDL-CF [150 ± 71 mg/dL (3.9 ± 1.8 mmol/L)] and LDL-CM/H levels [151 ± 70 mg/dL (6.1 ± 1.8 mmol/L); P = 0.746] were similar, whereas LDL-CLp(a)corM/H levels were significantly lower than LDL-CF [121 ± 62 mg/dL (3.1 ± 1.6 mmol/L); P < 0.001]. Target achievement as per latest guidelines in treated patients using the LDL-CM/H (2.5%) and especially LDL-CLp(a)corM/H methods (10.7%) were significantly different than LDL-CF (2.9%; P < 0.001). In children, all 3 formulas resulted in similar LDL-C levels, both at diagnosis and in treated patients. However, target achievement by LDL-CF was lower compared with LDL-CM/H and LDL-CLp(a)corM/H methods (22.1 vs 24.8 vs 33.3%; P < 0.001 for both comparisons). CONCLUSION: LDL-CLp(a)corM/H results in significantly lower values and higher target achievement rate in both treated adults and children. If validated in clinical trials, LDL-CLp(a)corM/H may become the method of choice to more accurately estimate 'true' LDL-C levels in FH patients.

Recent developments in pharmacotherapy for hypertriglyceridemia: what's the current state of the art?

Introduction: Hypertriglyceridemia is associated with both the development of cardiovascular disease (CVD) when mild-to-moderate and high risk of pancreatitis when more severe. The residual CVD risk after low-density lipoprotein cholesterol (LDL-C) lowering is, in part, attributed to high triglyceride (TG) levels. Therefore, there appears to be a need for effective TG-lowering agents.Areas covered: This review presents the most recent advances in hypertriglyceridemia treatment; specifically, it discusses the results of clinical trials and critically comments on apolipoprotein C-III inhibitors, angiopoietin-like 3 inhibitors, alipogene tiparvovec, pradigastat, pemafibrate and novel formulations of omega-3 fatty acids.Expert opinion: In the era of extreme lowering of LDL-C levels with several agents, there seems to be space for novel therapeutic options to combat parameters responsible for residual CVD risk, among which are elevated TGs. Furthermore, a significant number of individuals have very high TG levels and encounter the risk of acute pancreatitis. The most recently developed TG-lowering drugs appear to have a role in both conditions; the choice is mainly based on baseline TG levels. Dyslipidemia guidelines are likely to change in the near future to include some of these agents. Of course, long-term data regarding their safety and efficacy in terms of CVD outcomes and pancreatitis are warranted.

Drug-Induced Hypophosphatemia: Current Insights.

Phosphate is actively involved in many important biochemical pathways, such as energy and nucleic acid metabolism, cellular signaling, and bone formation. Hypophosphatemia, defined as serum phosphate levels below 2.5 mg/dL (0.81 mmol/L), is frequently observed in the course of treatment with commonly used drugs, such as diuretics, bisphosphonates, antibiotics, insulin, and antacids. Furthermore, this undesired effect may complicate the use of several novel medications, including teriparatide, denosumab, parenteral iron, and antiviral and antineoplastic agents. This review addresses drug-associated hypophosphatemia, focusing on underlying mechanisms and the most recent knowledge on this topic, in order to increase the insight of clinicians, with reference to early diagnosis and appropriate management.

No effect of fenugreek, bergamot and olive leaf extract on glucose homeostasis in patients with prediabetes: a randomized double-blind placebo-controlled study.

INTRODUCTION: The main pathophysiologic mechanism of type 2 diabetes (T2D) is insulin resistance, which exists several years before T2D diagnosis. The term 'prediabetes' applies to patients with insulin resistance but without overt T2D. The improvement of glucose homeostasis in these patients may prevent or delay the development of T2D and its complications. Data suggest that fenugreek, olive leaf polyphenols and bergamot extract may improve carbohydrate metabolism. We examined the effect of an agent containing fenugreek, olive leaf polyphenols and bergamot extract (active agent) on glucose homeostasis in patients with prediabetes. MATERIAL AND METHODS: This was a single-center, randomized, double-blind, placebo-controlled trial; patients with prediabetes (N = 100) were randomized to treatment with the active agent or placebo. The primary efficacy endpoint was the change in glycated hemoglobin (HbA1c) at 6 months after treatment initiation. Secondary endpoints included changes in other parameters of glucose metabolism and lipid profile. RESULTS: Overall 87 patients completed the study. No significant change in HbA1c was observed in either treatment group. Similarly, fasting plasma glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR) index and lipid profile remained unaltered in both groups. CONCLUSIONS: The administration of an agent containing fenugreek, olive leaf polyphenols and bergamot extract for 6 months did not improve glycemia or lipid parameters in patients with prediabetes.

Significant Weight Loss in a Patient Taking Olmesartan: An Unusual Case Report.

OBJECTIVE: Olmesartan-induced enteropathy consists a syndrome that mimics celiac disease both clinically and histologically. Cases of this entity have sporadically been reported since 2012 and are usually characterized by severe diarrhea and malabsorption, followed by significant weight loss. CASE REPORT: Herein, we report an uncommon case of this syndrome, where weight loss preceded several months the onset of gastrointestinal symptoms. DISCUSSION AND CONCLUSION: Physicians should be aware of unexplained weight loss in patients taking olmesartan, as prompt discontinuation of the drug may prevent the deleterious consequences of malabsorption.